Hauben, et al. (2001): Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease

[Wise Young]

• Hauben E, Agranov E, Gothilf A, Nevo U, Cohen A, Smirnov I, Steinman L and Schwartz M (2001). Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease. J Clin Invest. 108 (4): 591-9. Summary: Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin- associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin- derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11518733
http://www.jci.org/cgi/content/full/108/4/591
http://www.jci.org/cgi/content/abstract/108/4/591> Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.

[This message was edited by Wise Young on September 23, 2001 at 10:32 PM.]

[Wise Young]

This is the work of Michal Schwartz where she activated t-lymphocytes by exposing them to myelin proteins and then injected these cells into rats after spinal cord injury. This resulted in improved recovery up to a week after injury. This has greatly fascinated the scientific community. The explanation of this is not clear. Wise.